Evidence map›Paper›PMID 38177315›Full record

ArticleThe EMBO journal2024

Using CombiCells, a platform for titration and combinatorial display of cell surface ligands, to study T-cell antigen sensitivity modulation by accessory receptors.

Ashna Patel, Violaine Andre, Sofia Bustamante Eguiguren, Michael I Barton, Jake Burton, Eleanor M Denham, Johannes Pettmann, Alexander M Mørch, Mikhail A Kutuzov, Jesús A Siller-Farfán and 3 more

Open access · hybridAbstract read
In one paragraph

Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
5.0field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. CAR-modified marrow infiltrating lymphocytes efficiently target malignant plasma cells with very low antigen density.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 1 institution in 3 countries.

Ashna PatelSir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.ORCID http://orcid.org/0009-0008-4502-3990
Violaine AndreSir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.
Sofia Bustamante EguigurenSir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.
Michael I BartonSir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.ORCID http://orcid.org/0000-0002-9263-6481
Jake BurtonSir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.
Eleanor M DenhamSir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.
Johannes PettmannSir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.
Alexander M MørchThe Kennedy Institute of Rheumatology, University of Oxford, Oxford, OX3 7FY, UK.ORCID http://orcid.org/0000-0002-1881-2424
Mikhail A KutuzovSir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.ORCID http://orcid.org/0000-0003-3386-4350
Jesús A Siller-FarfánSir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.
Michael L DustinThe Kennedy Institute of Rheumatology, University of Oxford, Oxford, OX3 7FY, UK.ORCID http://orcid.org/0000-0003-4983-6389
P Anton van der MerweSir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.ORCID http://orcid.org/0000-0001-9902-6590
Omer DushekSir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK. omer.dushek@path.ox.ac.uk.ORCID http://orcid.org/0000-0001-5847-5226
University of Oxford · GB

Funding

UKRI | Biotechnology and Biological Sciences Research Council (BBSRC) (BB/M011224/1Wellcome TrustWellcome Trust (WT) (108869/Z/15/ZWellcome Trust (WT) 207537/Z/17/Z
6 · The paper itself

Abstract

Understanding cellular decisions due to receptor-ligand interactions at cell-cell interfaces has been hampered by the difficulty of independently varying the surface density of multiple different ligands. Here, we express the synthetic binder protein SpyCatcher, designed to form spontaneous covalent bonds with interactors carrying a Spytag, on the cell surface. Using this, we show that addition of different concentrations and combinations of native Spytag-fused ligands allows for the combinatorial display of ligands on cells within minutes. We use this combinatorial display of cell surface ligands-called CombiCells-to assess T cell antigen sensitivity and the impact of T cell co-stimulation and co-inhibition receptors. We find that the T cell receptor (TCR) displayed greater sensitivity to peptides on major-histocompatibility complexes (pMHC) than synthetic chimeric antigen receptor (CARs) and bi-specific T cell engager (BiTEs) display to their target antigen, CD19. While TCR sensitivity was greatly enhanced by CD2/CD58 interactions, CAR sensitivity was primarily but more modestly enhanced by LFA-1/ICAM-1 interactions. Lastly, we show that PD-1/PD-L1 engagement inhibited T cell activation triggered solely by TCR/pMHC interactions, as well as the amplified activation induced by CD2 and CD28 co-stimulation. The ability to easily produce cells with different concentrations and combinations of ligands should accelerate the study of receptor-ligand interactions at cell-cell interfaces.

Indexed as

AntigensT-LymphocytesLigandsLymphocyte ActivationReceptors, Antigen, T-CellAntigensLigandsReceptors, Antigen, T-CellCell–Cell RecognitionChimeric Antigen ReceptorsReceptor/Ligand InteractionsSurface Ligand PresentationT Cell Antigen Sensitivity

Identifiers

PMID38177315
PMCPMC10897201
OpenAlexW4389941184

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.